Cancer vaccines are emerging as important tools for cancer treatment and prevention. Unfortunately, the cohorts that ultimately will benefit most from the vaccines, those at elevated risk for cancer, are likely to be stressed. Chronic stress can impair immune function, including immune response to vaccines. An inadequate response to vaccines can weaken their protective effect ;1 however, the mechanism by which stress exerts its effect on vaccine response is not known. One mechanism may involve stress-related increases in cortisol leading to decrements in B lymphocyte number. B lymphocytes are important for vaccine response. The immune system responds to invading pathogens (and vaccines) with a well-orchestrated cascade of events that involve a variety of immune cells and ultimately result in the production of antibodies by mature plasma cells of the B lymphocyte lineage. Previous work by our group has shown that high levels of academic stress are associated with very low numbers of peripheral blood B lymphocytes. There is ample in vitro and in vivo evidence that high levels of glucocorticoids cause reductions in B lymphocytes in mice. There is ample evidence that high levels of stress are associated with elevated cortisol levels in humans, but the evidence regarding cortisol causing reductions in B lymphocytes in humans is limited. There are only in vitro data to suggest high levels of cortisol in bone marrow cultures are associated with reductions in early B lymphocytes. To our knowledge, there are no in vivo human studies reporting increases in cortisol due to psychological stress are associated with dramatic decrements in B lymphocyte number. The purpose of the present biobehavioral research is to fill this gap with a longitudinal study of the effects of academic stress on salivary cortisol and B lymphocyte number among 40 comparison participants and 40 students over the course of their first year of graduate school which culminates with the qualifying examinations. These data will provide excellent preliminary data to support a larger grant application studying psychological stress, cortisol, B lymphocyte number, and antibody response to vaccine. Relevance of the present research to public health: Cancer vaccines are emerging as important tools for cancer treatment and prevention. But psychological stress can impair immune response to vaccine, and the people who will benefit most from cancer vaccines, those at genetic risk for cancer, are likely to be stressed. The present study will begin to elucidate the mechanism by which psychological stress impairs immune response to vaccines. [unreadable] [unreadable] [unreadable]